Expression and actions of GnIH and its orthologs in vertebrates: Current status and advanced knowledge
Abstract
The physiology of reproduction is very complex and is regulated by multiple factors, including a number of hypothalamic neuropeptides. In last few decades, various neuropeptides have been discovered to be involved in stimulation or inhibition of reproduction. In 2000, Tsutsui and colleagues uncovered gonadotropin-inhibitory hormone (GnIH), a neuropeptide generating inhibitory drive to the reproductive axis, in the brain of Coturnix quail. Afterward, GnIH orthologs were discovered in other vertebrates from fish to mammals including human. In these vertebrates, all the discovered GnIH and its ortholgs have LPXRFamide (X=L or Q) sequence at C-terminus. GnIH orthologs of mammals and primates are also termed as RFamide-related peptide (RFRP)-1 and -3 that too have an LPXRFamide (X=L or Q) motif at their C-terminus. GnIH and its orthologs form a member of the RFamide peptide family. GnIH signals via its canonical G protein coupled receptor 147 (GPR147). Both GnIH and GPR147 are expressed in hypothalamus and other brain regions. Besides actions through the hypothalamic GnRH and kisspeptinergic neurons, GnIH-GPR147 signaling exerts inhibitory effect on the reproductive axis via pituitary gonadotropes and directly at gonadal level. Various factors including availability and quality of food, photoperiod, temperature, social interaction, various stresses and some diseases modulate GnIH-GPR147 signaling. In this review, we have discussed expression and actions of GnIH and its orthologs in vertebrates. Special emphasis is given on the role of GnIH-GPR147 signaling pathway in the regulation of reproduction. We have also reviewed and discussed currently available literature on the participation of GnIH-GPR147 signaling pathway in the stress modulation of reproduction.
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In vertebrate models, stress-induced glucocorticoids repress the HPG axis by inhibiting GnRH neurons or stimulating neurons releasing GnIH.
“In vertebrate models, stress-induced glucocorticoids repress the HPG axis by inhibiting GnRH neurons or stimulating neurons releasing gonadotropin-inhibitory hormone (GnIH) [89–91].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [89]
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“There are many studies on the mechanism of GnIH reproductive regulation, but almost of them focus on the hypothalamic-pituitary level, while there are very few studies related to the role of GnIH directly at the gonadal level (Bentley et al., 2008; Tsutsui et al., 2012; Tsutsui et al., 2015; Ullah et al., 2016).”
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“Moreover, the field has also started to appreciate that various functionalities of RFRPs are affected by various factors, including social interactions (4), photoperiod (5), temperature (6), food (7), and some diseases (8) in ovarian developmental periods.”
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BindingDB (2022) · UC San Diego · doi:10.7270/q2sj1qc8
- Authors
- Ullah, R., Shen, Y., Zhou, Y.-D., Huang, K., Fu, J.-F., Wahab, F., & Shahab, M.
- Affiliations
- Quaid-i-Azam University (PK)
- Zhejiang University (CN)
- German Primate Center (DE)
- Corresponding author
- Shahab, Muhammad
- Venue
- Neuropeptides
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 59
- Pages
- 9-20
- ISSN
- 0143-4179 (ISSN-L)
- OpenAlex
- W2399658045
- Cited by
- 30
- References
- 156
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 2
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropeptides (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Quaid-i-Azam University Research Fund
- Higher Education Commission of Pakistan
- National Natural Science Foundation (81570759, 81270938)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- gonadotropin-inhibitory hormone, RFamide-related peptides, RFRP-3, GPR147, hypothalamic neuropeptides, kisspeptin, GnRH neurons, gonadotrophs, photoperiod, food availability, vertebrate reproduction
- MeSH terms
- Animals, Coturnix, Female, Humans, Hypothalamic Hormones, Hypothalamus, Neurons, Neuropeptides, Pituitary Gland, Reproduction, Signal Transduction
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